Selenium Attenuates TBHP-Induced Apoptosis of Nucleus Pulposus Cells by Suppressing Mitochondrial Fission through
Peng Wang1, Shuo Zhang1, Weijian Liu1
1Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Abstract:
Intervertebral disc (IVD) degeneration (IDD), the leading cause of low back pain (LBP), remains intractable due to a lack of effective therapeutic strategies. Several lines of studies have documented that nucleus pulposus cell (NPC) death induced by excessive oxidative stress is a crucial contributor to IDD. However, the concrete role and regulation mechanisms have not been fully clarified. Selenium (Se), a vital prosthetic group of antioxidant enzymes, is indispensable for maintaining redox homeostasis and promoting cell survival. However, no light was shed on the role of Se on IDD progression, especially regulation on mitochondrial dynamics and homeostasis. To fill this research gap, the current study focuses on the effects of Se, including sodium selenite (SS) and selenomethionine (Se-Met), on IDD progression and the underlying mechanisms. In vitro, we found that both SS and Se-Met alleviated tert-butyl hydroperoxide- (TBHP-) induced oxidative stress, protected mitochondrial function, and inhibited apoptosis of NPCs. Further experiments indicated that Se suppressed TBHP-induced mitochondrial fission and rescued the imbalance of mitochondrial dynamics. Promoting mitochondrial fission by carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP) partially counteracted the cytoprotective effects of Se. Moreover, blocking nuclear factor erythroid 2-related factor 2 (Nrf2) with ML385 proved that the effect of Se on regulating mitochondrial dynamics was attributed to the activation of the Nrf2 pathway. In the puncture-induced rat IDD model, a supplement of Se-Met ameliorated degenerative manifestations. Taken together, our results demonstrated that Se suppressed TBHP-induced oxidative stress and mitochondrial fission by activating the Nrf2 pathway, thereby inhibiting the apoptosis of NPCs and ameliorating IDD. Regulation of mitochondrial dynamics by Se may have a potential application value in attenuating the pathological process of IDD.
Insights
Selenium (Se) supplementation mitigates intervertebral disc degeneration (IDD) by reducing oxidative stress and improving mitochondrial function. This study reveals Se activates the Nrf2 pathway, protecting nucleus pulposus cells (NPCs) from apoptosis and ameliorating IDD progression.
Area of Science:
- Biochemistry
- Cell Biology
- Biomedical Engineering
Background:
- Intervertebral disc degeneration (IDD) is a primary cause of low back pain, often driven by nucleus pulposus cell (NPC) death due to oxidative stress.
- Current therapeutic strategies for IDD are limited, highlighting the need for novel treatments targeting cellular mechanisms.
- Selenium (Se), an essential antioxidant, plays a role in redox homeostasis, but its specific effects on IDD, particularly mitochondrial dynamics, remain unclear.
Purpose of the Study:
- To investigate the therapeutic effects of selenium (Se) on intervertebral disc degeneration (IDD) and elucidate its underlying mechanisms.
- To examine how Se, including sodium selenite (SS) and selenomethionine (Se-Met), influences oxidative stress, mitochondrial dynamics, and apoptosis in nucleus pulposus cells (NPCs).
- To determine the role of the Nrf2 pathway in Se-mediated protection against IDD.
Main Methods:
- In vitro studies using tert-butyl hydroperoxide (TBHP) to induce oxidative stress in NPCs, assessing the effects of SS and Se-Met on cell viability, mitochondrial function, and apoptosis.
- Mitochondrial dynamics were evaluated by analyzing mitochondrial fission and fusion, with interventions using carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP) and ML385 (Nrf2 inhibitor).
- An in vivo rat model of puncture-induced IDD was used to assess the therapeutic efficacy of Se-Met supplementation on degenerative changes.
Main Results:
- Both SS and Se-Met demonstrated protective effects by alleviating TBHP-induced oxidative stress, preserving mitochondrial function, and inhibiting NPC apoptosis.
- Se was found to suppress TBHP-induced mitochondrial fission and restore mitochondrial dynamics, with FCCP partially reversing these protective effects.
- Activation of the Nrf2 pathway by Se was confirmed as the mechanism for regulating mitochondrial dynamics, as blocking Nrf2 with ML385 counteracted Se's effects.
- Se-Met supplementation in a rat IDD model significantly ameliorated degenerative manifestations.
Conclusions:
- Selenium (Se) effectively suppresses oxidative stress and mitochondrial fission in intervertebral disc degeneration (IDD) by activating the Nrf2 pathway.
- Se protects nucleus pulposus cells (NPCs) from apoptosis and mitigates IDD progression, suggesting a potential therapeutic role.
- The regulation of mitochondrial dynamics by Se offers a promising avenue for developing novel strategies to treat IDD.
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